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Pigozzi, Barbara (2008) Eziopatogenesi e terapia dell'acne:
studio epidemiologico delle caratteristiche cliniche di una popolazione di pazienti affetti da acne e analisi dei polimorfismi del gene codificante per il recettore degli androgeni e del gene codificante per il citocromo P-450 1A1.
[Ph.D. thesis]

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Abstract (english)

Acne vulgaris is a chronic inflammatory disease of the pilosebaceous follicles, which are located on the face, neck, chest, upper back, and upper arms. It is a pleomorphic disorders with multifactorial pathogenesis. Typically, lesions range from open and closed comedones to inflammatory papules, pustules, cysts, nodules and scarring may result.
Acne vulgaris is the most common skin disorders.
The pathogenesis of acne centers on the interaction of sebaceous hyperplasia, follicular hyperkeratinization, proliferation of Propionibacterium acnes, inflammation and immune reaction. But the aetiology is already understand and the evolution, severity and response to treatment are subject to variations. Some studies have shown the importance of genetic factors in the pathogenesis of acne, but the role of heredity on acne severity and response to treatment remains unclear.
The role of androgens is well established and their action is mediated by the androgen receptor. The amino-terminal domain of this receptor, is required for transcriptional activation and contains a region of polyglutamine encoded by CAG trinucleotide repeats. In humans, the number of CAG repeats is polymorphic.
Recently some studies have shown an association between this polymorphism and acne and other androgens influence diseases, such as androgenetic alopecia, prostate cancer.
Other genetic studies have shown a relationship between polymorphisms in the Human cytochrome P-450 1A1 gene (CYP1A1) and acne. The cytochrome P-450 1A1 is one of the most active enzymes involved in retinoids metabolism. Retinoids are morphogenic for the sebaceous gland. In a recent study it has been signalled in acne patients a high frequency of the thymine-to-cytosine (T-to-C) transition situated at position 6235 creating an additional cleavage site for MspI.
In order to improve the treatment of patients, prognostic factors of acne severity and evolution must be studied.
Systematic assessment of the severity of acne continues to challenge the clinician. Acne is a pleomorphic disorder of variable course and anatomical distribution. For these reasons, no system has been accepted universally.

The aim of our study was to analyze some clinic and epidemiologic features of patients affected by acne vulgaris to try to understand what role they can play in the pathogenesis of acne and if they can be prognostic factors of acne severity.
Second goal is validation of a grading system of severity, which features are accuracy and reproducibility and that can be used also by practicing clinicians.
Third purpose of this study is to test for an association between acne and acne severity, and CAG repeat length in the androgen receptor gene, and CYP1A1 polymorphism.

Patients and Methods:
A descriptive, prospective epidemiological study was conducted from January 2005 to October 2007 . It concerned patients with acne referred to Pediatrics Department and Dermatology Department for treatment of acne. We included patients with mild, moderate or severe acne. Epidemiological and clinical data, such as sex, age, age at onset, prepubertal or not, menarche age, family history of acne (father, mother, both parents, brother or others), body mass index, concomitant diseases (focusing on endocrine conditions), extension of lesion at onset, type and extension of lesions, grading of severity, therapy were collected in a data base.
The severity of acne was recorded using Global Acne Grading System (GAGS), (Doshi et al.), Leeds technique (Cunliffe score), Global Evaluation Scale (GES) at first visit and, for some patients, at 3, 6, 12 months.
We developed another grading system ("differentiated GAGS"), modifying GAGS in order to obtain a score for the face and a score for the trunk.
Epidemiologic analysis was made using t-student, Pearson e Rho di Spearman tests by software SPSS.
The polymorphisms were studied with the use of polymerase chain reaction and sequencing for the androgen receptor gene, and restriction fragment length polymorphism for CYP1A1.
Comparisons of allele and haplotype frequencies between cases and controls were analyzed by c2-tests.

Results and conclusion:
210 patients, 122 females and 88 males, aged 10-39 years, affected by mild to severe acne, were included in this study. Female showed a earlier onset compared to males. We found a role of hereditary factors. Presenting both parents affected by acne did not correlated with severity of the disease but seems with its duration.
Late onset acne appears to be different and to be caused by dissimilar pathogenetic mechanisms. It's almost exclusive of female subjects and it's not correlated with hereditary factors.
Male hormones are responsible of acne manifestation especially in particular body areas.
Female subjects usually develop acne after menarche. Patients developing acne before menarche are prone to more severe truncal involvement.
For many reasons it's important to have a separate severity index for face and trunk. We developed the "Differentiated GAGS" scoring index, that significantly correlated with the Cunliffe score index obtained with the Leeds technique. Concerning the analysis of the two genetic factors in our study population, we found a promising role of CYP450 1A1 polymorphisms. Further studies are required to clarify the role of these genetic factors in the pathogenesis of acne.

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EPrint type:Ph.D. thesis
Tutor:Basso, Giuseppe
Supervisor:Belloni Fortina, Anna
Data di deposito della tesi:January 2008
Anno di Pubblicazione:January 2008
Key Words:eziopatogenesi acne, polimorfismo recettore degli androgeni, polimorfismo CYP1A1
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/35 Malattie cutanee e veneree
Struttura di riferimento:Dipartimenti > pre 2012 - Dipartimento di Pediatria
Codice ID:535
Depositato il:02 Oct 2008
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1. Tan JK, Vasey K, Fung KY. Beliefs and perceptions of patients with acne. J Am Acad Dermatol 2001; 44: 439-45. Cerca con Google

2. Smithard A, Glazebrook C, Williams HC. Acne prevalence, Knowledge about acne and psychological morbidity in mid-adolescence: a community-based study. Br J Dermatol 2001; 145: 274-9. Cerca con Google

3. Aktan S, Ozmen E, Sanli B. Anxiety, depression, and nature of acne vulgaris in adolescents. Int J Dermatol 2000; 39: 354-7. Cerca con Google

4. White MG. Recent findings in the epidemiologic evidence, classification, and subtypes of acne vulgaris. J Am Acad Dermatol 1998; 39: S34-7. Cerca con Google

5. Mills CM, Peters TJ, Finlay AY. Does smoking influence acne? Clin Exp Dermatol 1993; 18: 100-1. Cerca con Google

6. Schafer T, Nienhaus A, Vieluf D, Berger J, Ring J. Epidemiology of acne in the general population: the risk of smoking. Br J Dermatol 2001; 145: 100-4. Cerca con Google

7. Knaggs HE, Holland DB, Morris C, Wood EJ, Cunliffe WJ. Quantification of cellular proliferation in acne using the monoclonal antibody Ki-67. J Invest Dermatol 1994; 102:89-92. Cerca con Google

8. Cunliffe WJ, Holland DB, Clark SM, Stables GI. Comedogenesis: some new aetiological, clinical and therapeutic strategies. Br J Dermatol 2000; 142: 1084-91. Cerca con Google

9. Leyden JJ. New understandings of the pathogenesis of acne. J Am Acad Dermatol 1995; 32: 15-25. Cerca con Google

10. Stewart ME, Downing DT, Cook JS, Hansen JR, Strauss JS. Sebaceous gland activity and serum dehydroepiandrosterone sulphate levels in boys and girls. Arch Dermatol 1992; 128: 1345-8. Cerca con Google

11. Herane MI, Ando I. Acne in infancy and acne genetics. Dermatology 2003; 206: 24-8. Cerca con Google

12. Imperato-McGinley J, Gautier T, Cai LQ, Yee B, Epstein J, Pochi P. The androgen control of sebum production. Studies of subjects with dihydrotestosterone deficiency and complete androgen insensitivity. J Clin Endocrinol Metabol 1993; 76: 524-8. Cerca con Google

13. Thiboutot D, Gilliland K, Light J, Lookingbill D. Androgen metabolism in sebaceous glands from subjects with and without acne. Arch Dermatol 1999; 135: 1041-5. Cerca con Google

14. Thiboutot D. Hormones and acne: pathophysiology, clinical evaluation, and therapies. Seminars in Cutaneous Medicine and Surgery 2001; 20: 144-53. Cerca con Google

15. Burkhart CG, Burkhart CN, Lehmann PF. Acne: a review of immunologic and microbiologic factors. Postgrad Med J 1999; 75: 328-31. Cerca con Google

16. Ingham E, Walters CE, Eady EA, Cove JH, Kearney JN, Cunliffe WJ. Inflammation in acne vulgaris: failure of skin micro-organisms to modulate keratinocyte interleukin 1a production in vitro. Dermatology 1998; 196: 86-8. Cerca con Google

17. Holland KT, Aldana O, Bojar RA, Cunliffe WJ, Eady EA, Holland DB, Ingham E, McGeown C, Till A, Walters C. Propionibacterium acnes and acne. Dermatology 1998; 196: 67-8. Cerca con Google

18. Guy R, Kealey T. Modelling the infundibulum in acne. Dermatology 1998; 196: 32-7. Cerca con Google

19. Downing DT, Stewart ME, Wertz PW, Strauss JS. Essential fatty acids and acne. J Am Acad Dermatol 1986; 14: 221-5. Cerca con Google

20. Oberemok SS, Salita AR. Acne vulgaris, I: pathogenesis and diagnosis. Cutis 2002; 70:101-5. Cerca con Google

21. Kim J, Ochoa MT, Krutzik SR, Takeuchi O, Uematsu S, Legaspi AJ, Brightbill HD, Holland D, Cunliffe WJ, Akira S, Sieling PA, Godowski PJ, Modlin RL. Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. J Immunol 2002; 169: 1535-41. Cerca con Google

22. Friedman GD. Twin studies of disease haritability based on medical records: application to acne vulgaris. Acta Genet Med Gemellol (Roma) 1984; 33: 487-95. Cerca con Google

23. Goulden V, McGeown CH, Cunliffe WJ. The familial risk of adult acne: a comparison between first-degree relatives of affected and unaffected individuals. Br J Dermatol 1999; 141: 297-300. Cerca con Google

24. Ballanger F, Baudry P, N'Guyen JM, Khammari A, Dréno B. Heredity: A Prognostic Factor for Acne. Dermatology 2006; 212: 145-9. Cerca con Google

25. Sawaya ME, Salita AR. Androgen receptor polymorphism (CAG repeat lengths) in androgenetic alopecia, hirsutism, and acne. J Cutan Med Surg 1998; 3: 9-15. Cerca con Google

26. Ellis JA, Stebbing M, Harrap SB. Polymorphism of the androgen receptor gene is associated with male pattern baldness. J Invest Dermatol 2001; 116: 452-5. Cerca con Google

27. Shibata A, Garcia MI, Cheng I, Stamey TA, McNeal JE, Brooks JD, Henderson S, Yemoto CE, Peehl DM. Polymorphism in the androgen receptor and type II 5a-reductase genes and prostate cancer prognosis. The Prostate 2002; 52: 269-78 Cerca con Google

28. Paraskevaidis A, Drakoulis N, Roots I, Orfanos CE, Zouboulis ChC. Polymorphisms in the Human Cytochrome P-450 1A1 Gene (CYP1A1) as a Factor for Developing Acne. Dermatology 1998; 196: 171-5. Cerca con Google

29. Cordain L, Lindeberg S, Hurtado M, Hill K, Eaton SB, Brand-Miller J. Acne vulgaris: a disease of Western civilization. Arch Dermatol 2002; 138: 1584-90. Cerca con Google

30. Adebamowo CA, Spiegelman D, Danby FW, Frazier AL, Willet WC, Holmes MD. High school dietary daily intake and teenage acne. J Am Acad Dermatol 2005; 52:207-14. Cerca con Google

31. Danby FW. Acne and milk, the diet myth, and beyond. J Am Acad Dermatol 2005; 52:360-2. Cerca con Google

32. Shalita AR. Clinical aspects of acne. Dermatology 1998; 196: 93-4. Cerca con Google

33. Witkowski JA, Parish LC, Guin JD. Acne grading methods. Arch Dermatol 1980; 116: 517-8. Cerca con Google

34. Burke BM, Cunliffe WJ. The assessment of acne vulgaris - the Leeds technique. Br J Dermatol 1984; 111: 83-92. Cerca con Google

35. Doshi A, Zaheer A, Stiller MJ. A comparison of current acne grading systems and proposal of a novel system. Int. J Dermatol 1997; 36: 416-8. Cerca con Google

36. Gollnick H, Cunliffe W, Berson D, Dreno B, Finlay A, Leyden JJ et al. Management of acne. J Am Acad Dermatol 2003; 49 (Suppl 1): S1-37. Cerca con Google

37. Walton S, Wyatt EH, Cunliffe WJ: Genetic control of sebum excretion and acne. A twin study. Br J Dermatol 1998; 118: 393-6. Cerca con Google

38. Bataille V, Snieder H, MacGregor AJ, et al: The influence of genetics and environmental factors in the pathogenesis of acne: a twin study of acne in women. J Invest Dermatol 2002; 119: 1317-22. Cerca con Google

39. Amado JM, Matos ME, Abreu AM, Loureiro L, Oliveira J, Verde A, Massa A. The prevalence of acne in the north of Portugal. J European Academy of Dermatology and Venereology 2006; 20: 1287-95. Cerca con Google

40. Lucky AW, Biro FM, Simbarti LA, Morrison JA, Sorg NW. Predictors of severity of acne vulgaris in young adolescent girls: Results of a five-year longitudinal study. The Journal of Pediatrics 1997; 130: 30-9. Cerca con Google

41. Burton JL, Cunliffe WJ, Stafford I, Shuster S. The prevalence of acne in adolescence. Br J Dermatol 1971; 85: 119-26. Cerca con Google

Monografie Cerca con Google

1. Innocenzi D. Acne giovanile: problematiche attuali. J. Medical Books Edizioni. 2004. Cerca con Google

2. Fabbri P. Acne. Pacini editore. 2007. Cerca con Google

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